The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer

Abstract

The mitogen-activated protein kinase (MAPK) family is an important bridge in the transduction of extracellular and intracellular signals in different responses at the cellular level. Within this MAPK family, the p38 kinases can be found altered in various diseases, including cancer, where these kinases play a fundamental role, sometimes with antagonistic mechanisms of action, depending on several factors. In fact, this family has an immense number of functionalities, many of them yet to be discovered in terms of regulation and action in different types of cancer, being directly involved in the response to cancer therapies. To date, three main groups of MAPKs have been identified in mammals: the extracellular signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), and the different isoforms of p38 (α, β, γ, δ). In this review, we highlight the mechanism of action of these kinases, taking into account their extensive regulation at the cellular level through various modifications and modulations, including a wide variety of microRNAs. We also analyze the importance of the different isoforms expressed in the different tissues and their possible role as biomarkers and molecular targets. In addition, we include the latest preclinical and clinical trials with different p38-related drugs that are ongoing with hopeful expectations in the present/future of developing precision medicine in cancer.

Theaflavin-3,3 ′ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

“…Additionally, ROS are involved in the MAPK pathway, which modulates signal transduction and is associated with many biological functions, such as proliferation, survival, and apoptosis [ 37 – 39 ]. MAPK signalling is a double-edged pathway that can promote tumour progression and tumour cell death in vivo and in vitro [ 40 – 43 ]. The same phenomenon is also observed in osteosarcoma [ 44 – 49 ].…”

Pre exposure to enriched environment alleviates brain injury after ischemia-reperfusion by inhibiting p38MAPK/STAT1 pathway

“…Furthermore, although we have demonstrated that the p38 MAPK/STAT1 pathway is inextricably linked to the protection mediated by EE pretreatment, there is still a lot of meaningful work worth exploring and completing. First, p38 has four subtypes: p38 α, p38 β, p38 γ and p38 δ [47] (Fig. 7).…”

Cinnamomum zeylanicum Extract and its Bioactive Component Cinnamaldehyde Show Anti-Tumor Effects via Inhibition of Multiple Cellular Pathways

“…MAP kinase P38 alpha (MAPKP-38α) is a member of mitogen-activated protein kinases activated by various stimuli like heat shock, oxidative stress, inflammatory cytokines, damaged DNA, etc., ( Zeyen et al, 2022 ). It regulates cellular functions like division, stress response, differentiation, survival, and immune ( García-Hernández et al, 2021 ). The activation of MAPKP-38α by reactive oxygen species (ROS) in cancer cells ultimately leads to the apoptosis of cancer cells ( Dolado et al, 2007 ).…”